Distinct Frizzled receptors independently mediate endomesoderm specification and primary archenteron invagination during gastrulation in Nematostella

Author(s):  
Naveen Wijesena ◽  
Hongyan Sun ◽  
Shalika Kumburegama ◽  
Athula H. Wikramanayake
Keyword(s):  
2018 ◽  
Vol 96 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Ateeque Siddique ◽  
Bin Yu ◽  
Kashif Khan ◽  
Ryan Buyting ◽  
Hamood Al-Kindi ◽  
...  

The cellular mechanisms that induce calcific aortic stenosis are yet to be unraveled. Wnt signaling is increasingly being considered as a major player in the disease process. However, the presence of Wnt Frizzled (Fzd) receptors and co-receptors LRP5 and 6 in normal and diseased human aortic valves remains to be elucidated. Immunohistochemistry and quantitative polymerase chain reaction were used to determine Fzd receptor expression in normal and calcified human aortic valve tissue, as well as human aortic valve interstitial cells (HAVICs) isolated from calcified and normal human aortic valves. There was significantly higher mRNA expression of 4 out of the 10 Fzd receptors in calcified aortic valve tissues and 8 out of the 10 in HAVICs, and both LRP5/6 co-receptors in calcified aortic valves (P < 0.05). These results were confirmed by immunohistochemistry, which revealed abundant increase in immunoreactivity for Fzd3, 7, and 8, mainly in areas of lipid core and calcified nodules of diseased aortic valves. The findings of abundant expression of Fzd and LRP5/6 receptors in diseased aortic valves suggests a potential role for both canonical and noncanonical Wnt signaling in the pathogenesis of human aortic valve calcification. Future investigations aimed at targeting these molecules may provide potential therapies for aortic valve stenosis.


1997 ◽  
Vol 94 (7) ◽  
pp. 2859-2863 ◽  
Author(s):  
A. Rattner ◽  
J.-C. Hsieh ◽  
P. M. Smallwood ◽  
D. J. Gilbert ◽  
N. G. Copeland ◽  
...  

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4739-4748 ◽  
Author(s):  
A.N. Salic ◽  
K.L. Kroll ◽  
L.M. Evans ◽  
M.W. Kirschner

An expression cloning screen was used to isolate a novel gene homologous to the extracellular cysteine-rich domain of frizzled receptors. The gene (which we called sizzled for secreted frizzled) was shown to encode a soluble secreted protein, containing a functional signal sequence but no transmembrane domains. Sizzled (szl) is capable of inhibiting Xwnt8 as assayed by (1) dose-dependent inhibition of siamois induction by Xwnt8 in animal caps, (2) rescue of embryos ventralized by Xwnt8 DNA and (3) inhibition of XmyoD expression in the marginal zone. Szl can dorsalize Xenopus embryos if expressed after the midblastula transition, strengthening the idea that zygotic expression of wnts and in particular of Xwnt8 plays a role in antagonizing dorsal signals. It also suggests that inhibiting ventralizing wnts parallels the opposition of BMPs by noggin and chordin. szl expression is restricted to a narrow domain in the ventral marginal zone of gastrulating embryos. szl thus encodes a secreted antagonist of wnt signaling likely involved in inhibiting Xwnt8 and XmyoD ventrally and whose restricted expression represents a new element in the molecular pattern of the ventral marginal zone.


Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 577-586 ◽  
Author(s):  
H. Muller ◽  
R. Samanta ◽  
E. Wieschaus

Wingless signaling plays a central role during epidermal patterning in Drosophila. We have analyzed zygotic requirements for Wingless signaling in the embryonic ectoderm by generating synthetic deficiencies that uncover more than 99% of the genome. We found no genes required for initial wingless expression, other than previously identified segmentation genes. In contrast, maintenance of wingless expression shows a high degree of zygotic transcriptional requirements. Besides known genes, we have identified at least two additional genomic regions containing new genes involved in Wingless maintenance. We also assayed for the zygotic requirements for Wingless response and found that no single genomic region was required for the cytoplasmic accumulation of Armadillo in the receiving cells. Surprisingly, embryos homozygously deleted for the candidate Wingless receptor, Dfrizzled2, showed a normal Wingless response. However, the Armadillo response to Wingless was strongly reduced in double mutants of both known members of the frizzled family in Drosophila, frizzled and Dfrizzled2. Based on their expression pattern during embryogenesis, different Frizzled receptors may play unique but overlapping roles in development. In particular, we suggest that Frizzled and Dfrizzled2 are both required for Wingless autoregulation, but might be dispensable for late Engrailed maintenance. While Wingless signaling in embryos mutant for frizzled and Dfrizzled2 is affected, Wingless protein is still internalized into cells adjacent to wingless-expressing cells. Incorporation of Wingless protein may therefore involve cell surface molecules in addition to the genetically defined signaling receptors of the frizzled family.


2019 ◽  
Vol 20 (17) ◽  
pp. 4168 ◽  
Author(s):  
Mark Agostino ◽  
Sebastian Öther-Gee Pohl

Several proteins other than the frizzled receptors (Fzd) and the secreted Frizzled-related proteins (sFRP) contain Fzd-type cysteine-rich domains (CRD). We have termed these domains “putative Fzd-type CRDs”, as the relevance of Wnt signalling in the majority of these is unknown; the RORs, an exception to this, are well known for mediating non-canonical Wnt signalling. In this study, we have predicted the likely binding affinity of all Wnts for all putative Fzd-type CRDs. We applied both our previously determined Wnt‒Fzd CRD binding affinity prediction model, as well as a newly devised model wherein the lipid term was forced to contribute favourably to the predicted binding energy. The results obtained from our new model indicate that certain putative Fzd CRDs are much more likely to bind Wnts, in some cases exhibiting selectivity for specific Wnts. The results of this study inform the investigation of Wnt signalling modulation beyond Fzds and sFRPs.


Oncogene ◽  
2002 ◽  
Vol 21 (43) ◽  
pp. 6598-6605 ◽  
Author(s):  
Chae-Seo Rhee ◽  
Malini Sen ◽  
Desheng Lu ◽  
Christina Wu ◽  
Lorenzo Leoni ◽  
...  

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